To see the other types of publications on this topic, follow the link: Plasticity transmission.
Dissertations / Theses on the topic 'Plasticity transmission'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Plasticity transmission.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Trommershäuser, Julia. "A semi-microscopic model of synaptic transmission and plasticity." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=963474626.
Full text
2
Roberts, Lindsay A. "Plasticity related gene expression in the hippocampus." Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360278.
Full text
3
Gleizes, Marie. "Ectonucléotidases, adénosine et transmission synaptique." Thesis, Toulouse 3, 2017. http://www.theses.fr/2017TOU30306/document.
Full textAbstract:
Dans le cerveau, les fonctions de la phosphatase alcaline non spécifique des tissus (TNAP) ne sont pas clairement identifiées. La localisation et l'expression de cette enzyme au niveau neuronal suggère cependant, qu'elle joue un rôle important dans le développement et le fonctionnement du cerveau. Cela est supporté par la présence de graves crises d'épilepsie chez les humains porteurs d'une mutation de la TNAP. Ces crises d'épilepsie sont létales chez les souris KO pour la TNAP. Des études chez la souris montrent que la TNAP pourrait réguler l'inhibition postsynaptique médiée par le GABA et elle pourrait être impliquée dans l'inhibition présynaptique médiée par l'adénosine. L'adénosine est, en partie, synthétisée via la déphosphorylation successive de l'ATP en ADP puis en AMP par des ectonucléotidases. Parmi elles, la TNAP et l'ecto- 5'-nucléotidase (NT5E) catalysent l'hydrolyse de l'AMP en adénosine dans le cortex cérébral. L'adénosine agit principalement au niveau présynaptique par l'intermédiaire des récepteurs A1. Ainsi l'adénosine a une influence sur la transmission synaptique et sur la plasticité synaptique. Ceci pourrait expliquer, en partie, les crises d'épilepsie observées chez les souris KO pour la TNAP. Les deux objectifs principaux de ma thèse ont été : (1) évaluer la contribution de la TNAP dans la production d'adénosine dans le cerveau ; (2) étudier l'influence de l'adénosine sur la plasticité synaptique. Premièrement, l'étude de la contribution de la TNAP dans la production d'adénosine dans le cerveau a été réalisée au moyen de deux approches complémentaires. Une approche métabolomique (spectroscopie RMN du proton) sur des cerveaux entiers de souris KO pour la TNAP a permis de montrer que la TNAP participe, entre autre, à la synthèse d'adénosine dans le cerveau. Une deuxième approche, électrophysiologique sur tranches de cerveaux de souris in vitro, nous permet d'examiner les conséquences de l'inhibition des ectonucléotidases intervenant dans la synthèse de l'adénosine. Elle a révélé que l'inhibition des ectonucléotidases (TNAP et NT5E) ne supprime pas l'effet inhibiteur de l'AMP médiée par les récepteurs A1. Deuxièmement, nous avons étudié l'influence de l'adénosine sur la plasticité synaptique à courte terme. Nous avons enregistré des potentiels de champs dans la couche Ia du cortex piriforme en réponse à des stimulations électriques (3,125 à 100 Hz) présentée avec des fréquences recouvrant la gamme d'oscillations physiologiques. Nos résultats montrent qu'avec de fortes concentrations d'adénosine, la facilitation est accentuée par rapport à celle observée en situation contrôle. Cet effet est observé pour des fréquences supérieures ou égales à 25 Hz. De plus, cette accentuation est d'autant plus grande que la fréquence est élevée (maximum atteint à 100 Hz pour 100 µM). En bloquant l'action de l'adénosine endogène, l'effet contraire est observé : une facilitation déficitaire par rapport au contrôle et dont le défaut est croissant avec la fréquence de stimulation. Tous ces résultats convergent vers l'hypothèse qu'une déficience en TNAP, traduite par une absence d'adénosine, pourrait contribuer au maintien des processus épileptiques générés par un déséquilibre de l'inhibition et de l'excitation dû à une diminution de GABA. L'effet inhibiteur de l'AMP médié par les récepteurs A1 ne serait pas suffisant pour contrecarrer les crises d'épilepsie observées chez les sujets hypophosphatasiques et les souris KO pour la TNAPThe functions of Tissue Nonspecific Alkaline Phosphatase (TNAP) in the brain are not clearly identified. The localization and expression of TNAP at the neuronal level, however, suggests that it plays a prominent role in the development and the function in the brain. This is supported by the presence of severe epileptic seizures in humans carrying TNAP mutation. These epileptic seizures are lethal in TNAP KO mice. Studies in mice show that TNAP could regulate GABA-mediated postsynaptic inhibition and may be involved in presynaptic inhibition mediated by adenosine. Adenosine is, partly, synthesized via the successive dephosphorylation of ATP to ADP and then to AMP by ectonucleotidases. Among them TNAP and ecto-5'-nucleotidase (NT5E) are able to hydrolyze AMP into adenosine. Adenosine acts mainly at the presynaptic level via A1 receptors activation. Adenosine has an influence on synaptic transmission and thus on synaptic plasticity. This could partly explain the epileptic seizures observed in TNAP knock-out mice. The two main purposes of my thesis were: (1) to evaluate the contribution of TNAP in adenosine production in the brain; (2) to study the influence of adenosine on synaptic plasticity. Firstly, the study of the contribution of TNAP in adenosine production in the brain was carried out using two complementary approaches. A metabolomic approach (proton NMR spectroscopy) on whole brains of TNAP KO mice showed that TNAP in involved in adenosine synthesis in the brain. In a second approach, in vitro electrophysiological recordings on mouse brain slices allowed us to examine the consequences of the inhibition of the ectonucleotidases involved in adenosine synthesis. This revealed that inhibition of ectonucleotidases (TNAP and NT5E) did not suppress the inhibitory effect of AMP mediated by A1 receptors. Secondly, we studied the influence of adenosine on short-term synaptic plasticity. Field potentials were recorded in response to electrical stimulations (3.125 to 100 Hz) applied with frequencies encompassing the range of physiological oscillation. Our results show that, with high adenosine concentrations, the facilitation is emphasized compared to that observed in the control situation. This effect is observed for frequencies greater than or equal to 25 Hz. In addition, the higher the frequency, the greater the facilitation. Finally, by blocking the action of endogenous adenosine, the opposite effect was observed: a deficient facilitation with respect to the control, whose defect was increasing with stimulation frequency. All these results converge towards the hypothesis that TNAP deficiency, expressed by absence of adenosine, could contribute to the maintenance of the epileptic processes generated by an imbalance of the neuronal inhibition and the excitation due to a decrease of GABA. AMP inhibitory effect mediated by A1 receptors, would not be sufficient to counteract epileptic seizures observed in hypophosphatasic patients and TNAP KO mice
4
Vaccaro, V. "The role of presynaptic mitochondria in neuronal transmission and plasticity." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1468434/.
Full textAbstract:
Mitochondria are essential for cellular processes such as energy provision and Ca2 + buffering. Due to the highly polarized architecture of neurons, the positioning of mitochondria to areas of high activity is crucial for normal neuronal function. It has previously been shown that mitochondria are trafficked dependent upon neuronal activity. In this thesis, the role of mitochondria at the presynaptic terminal is investigated in order to determine whether the presence of mitochondria in turn influences neuronal transmission. Dual-colour live imaging reveals that terminals occupied by a mitochondrion show lower Ca2 + responses and that transmitter release is reduced. Furthermore, evidence for a role of activity-dependent positioning of mitochondria in homeostatic plasticity is shown, which is dependent upon the function of the Ca2 + -sensitive mitochondrial protein Miro1. Furthermore, the role of Miro1 in positioning mitochondria at presynaptic terminals is investigated in a knockout mouse system. This shows that calcium buffering seems to be changed in the Miro1 knockout neurons and that activity-dependent positioning of mitochondria to presynaptic terminals is affected. Taken together, this thesis examines the functions of mitochondria in the presynaptic terminal and sheds light on how their presence in the terminal may be regulated.
5
Fan, Kai Yoon. "GABAergic synaptic transmission, plasticity and integration in the subthalamic nucleus." Thesis, University of Sheffield, 2012. http://etheses.whiterose.ac.uk/3167/.
Full text
6
Ivanco, Tammy L. "Activity dependent plasticity in pathways between subcortical and cortical sites." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ30095.pdf.
Full text
7
Mercier, Marion. "Role of metabotropic glutamate receptor 8 in hippocampal synaptic transmission and plasticity." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665156.
Full textAbstract:
Group III metabotropic glutamate (mGlu) receptors (mGlu4/6/7/8) are presynaptic G-protein coupled receptors which act as auto- and hetero-receptors throughout the central nervous system. The development of mGlu8 receptor-selective agonist (S)-3,4-dicarboxyphenylglycine (DCPG), and antagonist (RS)-a-methyl-3,4- dicarboxyphenylglycine (MDCPG), in 2001 (Thomas et al., 2001), has led to a body of research investigating the possible function of this receptor subtype, and linking it to a number of pathological conditions including anxiety and epilepsy. The aim of the current work was to explore the role of mGlu8 within the hippocampal formation specifically, employing DCPG and MDCPG to assess its function in synaptic transmission and plasticity. The mGlu8-selectivity of these compounds was first assessed in the lateral perforant path (LPP) input to the dentate gyrus, a pathway known to express high levels of mGlu8 receptors. Field recordings in hippocampal slices from rat, and mGlu8 receptor knock-out (KO) mice revealed non-selective effects of DCPG at concentrations > 1 μM. Further experiments in slices from mGlu4, mGlu7 and mGlu2 KO mice, as well as a mGlu2-deficient substrain of Wistar rat, indicated that higher concentrations of the agonist activate the group II receptor subtype, mGlu2. Conversely, MDCPG appeared to be selective for mGlu8 at up to the highest concentration tested (30 μM). During this work in the LPP, DCPG was found to induce a novel form of mGlu8-mediated chemical long-term depression (LTD). This was induced by prolonged application of a high concentration (100 μM) of the agonist, and was more pronounced in older animals. Importantly, the LTD could be transiently reversed by application of MDCPG, up to two hours after washout of DCPG. Finally, patch-clamp recordings revealed inhibitory effects of DCPG on glutamatergic and GABAergic transmission onto subsets of CAl interneurons, but not pyramidal cells. This. is consistent with the known target-cell specific expression of mGlu8 within the hippocampus.
8
Jiang, Jianxiong Wooten Marie W. "Essential role for P62 in AMPA receptor trafficking and synaptic plasticity." Auburn, Ala, 2008. http://repo.lib.auburn.edu/EtdRoot/2008/SPRING/Biological_Sciences/Dissertation/Jiang_Jianxiong_41.pdf.
Full text
9
Sweeney, Yann Aodh. "Functional relevance of homeostatic intrinsic plasticity in neurons and networks." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/20982.
Full textAbstract:
Maintaining the intrinsic excitability of neurons is crucial for stable brain activity. This can be achieved by the homeostatic regulation of membrane ion channel conductances, although it is not well understood how these processes influence broader aspects of neuron and network function. One of the many mechanisms which contribute towards this task is the modulation of potassium channel conductances by activity-dependent nitric oxide signalling. Here, we first investigate this mechanism in a conductance-based neuron model. By fitting the model to experimental data we find that nitric oxide signalling improves synaptic transmission fidelity at high firing rates, but that there is an increase in the metabolic cost of action potentials associated with this improvement. Although the improvement in function had been observed previously in experiment, the metabolic constraint was unknown. This additional constraint provides a plausible explanation for the selective activation of nitric oxide signalling only at high firing rates. In addition to mediating homeostatic control of intrinsic excitability, nitric oxide can diffuse freely across cell membranes, providing a unique mechanism for neurons to communicate within a network, independent of synaptic connectivity. We next conduct a theoretical investigation of the distinguishing roles of diffusive homeostasis mediated by nitric oxide in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis robustly maintain stable activity. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that diffusive homeostasis interferes less than non-diffusive homeostasis in the synaptic weight dynamics of networks undergoing Hebbian plasticity. Overall, these results suggest a novel homeostatic mechanism for maintaining stable network activity while simultaneously minimising metabolic cost and conserving network functionality.
10
Liu, Zhi. "Unconventional forms of synaptic plasticity in the hippocampus and the striatum." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/2616.
Full textAbstract:
Synaptic transmission occurs as a result of either a spontaneous release of presynaptic vesicles or a batch release of presynaptic vesicles driven by action potentials. The physiological consequence of synaptic transmission driven by different patterns and frequencies of presynaptic stimulation has been extensively investigated. However, the physiological nature, mechanism as well as relevance of prolonged presynaptic stimulation have been poorly characterized. In this dissertation, I present three projects in which prolonged stimulation of synaptic transmission in different forms and different brain regions was studied for its effect on synaptic transmission, mechanisms and physiological relevance. In the first project, prolonged electrical stimulation (100 sec) at high frequency induced a deep synaptic depression in acute hippocampal slices, followed by a recovery of synaptic transmission after ~15 min. The deep synaptic depression was attributed to a complete depletion of presynaptic vesicle pools. In the second project, attempts were made to characterize the mechanism of nuclear activation of gene transcription induced by prolonged electrical stimulation (100 sec). Our results demonstrated that reduced inactivation of non-L-type calcium channels failed to provide calcium required for gene transcription, leaving the activation of gene transcription a selective function for L-type calcium channels. In the third project, we sought to study the physiological relevance of enhanced miniature events of inhibitory synapses induced by prolonged chemical stimulation. We showed that prolonged application (2 min) of nicotine to the striatal slice enhanced the frequency of miniature inhibitory currents that was accompanied with a reduction in the amplitude of evoked response. This reduction in the amplitude of evoked responses was ascribed to a compromised action potential invasion of presynaptic terminals possibly due to inactivation of sodium channels resulting from nicotine-induced depolarization. To summarize, prolonged stimulation of presynaptic vesicle release imposes significant influence upon neuron-to-neuron communication, with distinct mechanisms in different brain regions.
11
Guimond, Damien. "Les signaux extracellulaires modèlent la transmission GABAergique dans l'hippocampe en développement : le cas de la leptine." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4030/document.
Full textAbstract:
La présente thèse est liée à l'étude des indices externes au réseau neuronal et comment ceux-ci impactent le développement du système nerveux central. Spécifiquement, notre objectif était d'explorer l'effet de la leptine, une hormone sécrétée par les adipocytes, sur la plasticité développementale GABAergique. Nous avons utilisé des tranches aigues d'hippocampe de rat nouveau-né pour montrer que la leptine induit une potentialisation de la fréquence de l'activité miniature GABAergique, nécessitant une augmentation postsynaptique de calcium et l'activation de voies de signalisation spécifiques. Nous avons confirmé cet effet sur des cultures de neurones hippocampiques, sur lesquelles nous avons commencé à développer une méthode pour mesurer le corrélat morphologique de la plasticité fonctionnelle des synapses GABAergiques en culture. Cette approche suggère que la plasticité GABAergique induite par la leptine pourrait survenir à densité constante de récepteurs GABAA membranaires. La leptine induit donc une potentialisation de l'activité GABAergique dans les neurones hippocampiques en développement. Enfin, nous avons trouvé que les neurones pyramidaux de CA3 reçoivent une activité miniature GABAergique réduite chez des souris ob/ob ne produisant pas de leptine, suggérant que la leptine contribue au développement de la circuiterie GABAergique in vivo. Dans l'ensemble, les études que nous présentons apportent un éclairage nouveau sur le développement d'aires cérébrales dites de « haut niveau », dont nous avons observé qu'elles intègrent des signaux dits de « bas niveau », c'est-à-dire en provenance de la périphérie afin de modeler leur développementThe present dissertation tackles the larger question of how external cues impact the development of the central nervous system. Our specific aim was to explore the effect of leptin, an adipocyte-derived hormone, on GABAergic plasticity in the developing rodent hippocampus. We used acute hippocampal slices of newborn rats to show that leptin induces a long lasting potentiation of the frequency of miniature GABAergic activity. Using pharmacological tools we found that this event requires a postsynaptic increase in intracellular calcium as well as specific postsynaptic signaling pathways. To address the mechanistic action of leptin we confirmed the leptin-induced plasticity on hippocampal cultures and began to develop a method to measure the morphological correlate of GABAergic synapses in culture. Applying this method suggested that the leptin-induced GABAergic plasticity might occur with a constant density of postsynaptic GABAA receptor puncta. Taken together, these data show that leptin induces a potentiation of GABAergic activity in developing hippocampal neurons, perhaps by recruiting clusters of GABAA receptors expressed at the membrane to form newly functional GABAergic synapses. In addition we found that CA3 pyramidal neurons of leptin-deficient ob/ob mice exhibit lower miniature GABAergic activity compared to wild type littermates, which suggests that leptin contributes to the development of the hippocampal GABAergic circuitry in vivo. Overall, these studies shed a new light on the development of admittedly "higher-level" cerebral regions which were found here to integrate "lower-level", peripheral signals to shape their development
12
Vaughan, Sydney Katherine. "The role of Lynx1, an endogenous modulator of cholinergic transmission, in NMJ development, maintenance, and repair." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/100742.
Full textAbstract:
The cholinergic system drives muscle contraction and plays a central role in the formation, maintenance, and repair of mammalian neuromuscular junctions (NMJs) and skeletal muscles. Because of these essential actions, much effort has been devoted to identifying primary and auxiliary modulatory components of the cholinergic system at NMJs and throughout skeletal muscles. Here, I asked if Lynx1, a GPI-anchored protein shown to modulate nAChRs in the brain, is present and affects the activity of nAChRs at NMJs. Molecular and cellular analysis revealed that Lynx1 levels increase in skeletal muscles, specifically at NMJs, during development. Its expression pattern also closely mirrors changes in cholinergic transmission in vivo and in vitro. As expected, I found by co-immunoprecipitation that Lynx1 interacts with muscle nAChRs and using electrophysiology, I show that Lynx1 desensitizes nAChRs to ACh at NMJs. These findings demonstrate that Lynx1 regulates the cholinergic system at NMJs, suggesting roles for this gene in developing and adult NMJs. To determine the role of Lynx1 at NMJs, I examined Lynx1 knockout mice at different ages. While deletion of Lynx1 has no discernable effect on developing NMJs, its absence increases the incidence of NMJs with age-related morphological features, such as fragmentation and denervation, in young adult and middle-aged mice. Loss of Lynx1 also increases the number of slow-type muscle fibers in young and middle-aged mice, another hallmark of aging. Along with these morphological changes, deletion of Lynx1 affects expression of genes associated with NMJ stability, myogenesis, and muscle atrophy in young adult and middle-aged mice. Not surprisingly, the loss of Lynx1 reduces the density and stability of nAChRs at NMJs. Because of these findings, I surmised that loss of Lynx1 would adversely affect NMJs under other physiological stressors. However, I found the opposite as the loss of Lynx1 augments the capacity of NMJs to repair damages during exercise, following injury to motor axons, and during the initial symptomatic stage of amyotrophic lateral sclerosis (ALS). Since Lynx1 modulates the activity of nAChRs, these contrasting findings likely represent the positive and negative effects of heightened cholinergic transmission on aging compared to injury and disease-afflicted NMJs.Doctor of Philosophy
13
Bukalo, Olena. "The roles of extracellular matrix molecules in synaptic transmission and plasticity in the mouse hippocampus." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964891271.
Full text
14
Bhouri, Mehdi. "Plasticity of NMDA receptor-mediated transmission and metaplasticity in the CA1 region of the hippocampus." Thesis, University of Bristol, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702111.
Full textAbstract:
The hippocampus is a key structure of the brain for learning and memory processes. Two inputs to the CA1 region, the Schaffer collateral (SC) and the temporoammonic (TA) pathways, have different roles in these processes. N-methyl-D-aspartate receptors (NMDAR) are crucial for induction of synaptic plasticity and learning and memory processes, and are themselves subject to plasticity. Plasticity of NMDAR-mediated transmission can therefore change the threshold for induction of future synaptic plasticity and affect learning and memory. However, little is known about the effect of NMDAR-mediated plasticity on subsequent longterm potentiation (L TP) and long-term depression (L TO). In this study a combination of whole-cell recordings from CA1 pyramidal neurons and field recordings in the CA 1 area of the hippocampus was used to show that the SC-CA 1 input is subject to metaplasticity whereas the TA-CA1 input is not. Indeed L TO of NMDAR-mediated transmission is selectively induced in the SC pathway but not in the TA pathway. This LTD of NMDA EPSCs can prevent subsequent induction of L TP of AMPA receptor-mediated transmission via an increase of the threshold. The L TO of NMDAR-mediated transmission was shown to be mGlu1 receptor-dependent. However, LTD of AMPAR-mediated transmission in both inputs was not affected by the prior induction of L TO of NMDAR-mediated transmission. Therefore, these results show that the SC-CA 1 input can undergo meta plasticity whereas the TA-CA 1 input does not. These differences could explain the distinct roles of the two inputs in memory. In some neurodegenerative diseases such as Alzheimer's disease ,(AD) memory is impaired. AD is a tauopathy characterized by the aggregation of AB, a derivative of amyloid precursor protein (APP), and Tau, a microtubule-associated protein, which lead to synaptic loss and neuronal degeneration.
15
Birget, Philip Laurent Guillaume. "Evolutionary ecology of parasites : life-history traits, phenotypic plasticity, and reproductive strategies." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/28805.
Full textAbstract:
Adaptive phenotypic plasticity, the ability of a genotype to give rise to different phenotypes in different environments, evolves to allow organisms to fine-tune their life-history traits according to the varying conditions they encounter during their lives. Reproductive investment - the manner in which organisms divide their resources between survival and reproduction - is well studied in evolutionary ecology because it is a key determinant of fitness. However, whilst plasticity in reproductive effort is well understood for free-living multicellular taxa (such as insects, birds, and mammals), the application of evolutionary theory for plasticity and life history strategies to unicellular parasites and pathogens is lacking. In this thesis, I use empirical and theoretical approaches to uncover how differential resource allocation to non-replicating, sexual stages (gametocytes) versus asexually replicating stages can be harnessed by the rodent malaria parasite Plasmodium chabaudi to maximise its fitness across the often very variable conditions it encounters during infections. Differential allocation between those stages is equivalent to the fundamental life-history trade-off between survival and reproduction because gametocytes are responsible for between-host transmission (i.e. reproduction of the infection) whereas asexual parasites mediate host exploitation and within-host survival. A suite of within-host models reveal that malaria parasites could gain considerable fitness benefits in the face of low levels of drug treatment if they reduce their investment into gametocyte production ("reproductive restraint"), thereby assuring the continuity of the infection and capitalising on opportunities for future transmission. In contrast, high levels of drug treatment typically select parasites to commit all of their resources to gametocyte production ("terminal investment"), to escape a host that does not offer much opportunity for future transmission. My experiments reveal that P. chabaudi increases both its reproductive investment and its asexual replication rate in anaemic hosts (i.e. host that have a low density of red blood cells), suggesting that parasites profit from host anaemia and can afford high investment in gametocytes ("affluent investment"). I also uncover plasticity in a number of traits that underpin asexual replication rate, including invasion preference for different ages of red blood cells, but it is plasticity in the number of progeny (merozoites) per infected cell that is the main contributor to asexual replication rate. My experiments also reveal genetic variance in plasticity of the life-history traits investigated, which has profound implications for their evolution. Furthermore, plastic modification of these traits is associated with minimal costs or constraints, so that parasites can rapidly match life-history traits appropriately to the within-host environment. Severe anaemia is one of the deadliest symptoms of malaria, so observing that virulence and infectiousness increases in anaemic hosts has also fundamental clinical implications. Finally, the empirical and theoretical observations of affluent investment, reproductive restraint and terminal investment match theoretical predictions of how organisms should behave in varying environments, confirming P. chabaudi as a useful model system to test life-history theory.
16
Compans, Benjamin. "Rôle physiologique de l’organisation des récepteurs AMPA à l’échelle nanométrique à l’état basal et lors des plasticités synaptiques." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0700/document.
Full textAbstract:
Le cerveau est formé d’un réseau complexe de neurones responsables de nos fonctions cognitives et de nos comportements. Les neurones reçoivent via des contacts spécialisés nommés « synapses », des signaux d’autres neurones.[...] Le mécanisme par lequel les neurones reçoivent, intègrent et transmettent ces informations est très complexe et n'est toujours pas parfaitement compris. Dans les synapses excitatrices, les récepteurs AMPA (AMPARs) sont responsables de la transmission synaptique rapide. Les récents développements en microscopie de super résolution ont permis à la communauté scientifique de changer la vision de la transmission synaptique. Une première avancée fait suite à l’observation que les AMPARs ne sont pas distribués de façon homogène dans les synapses, mais sont organisés en nanodomaines de ~ 80 nm de diamètre contenant ~ 20 récepteurs. Ce contenu est un facteur important pour déterminer l'amplitude de la réponse synaptique. En raison de la basse affinité des AMPARs pour le glutamate, un AMPAR ne peut être activé que lorsqu'il est situé dans une zone de ~ 150 nm en face du site de libération des neurotransmetteurs. Récemment, il a été montré que les nanodomaines d’AMPARs sont situés en face de ces sites de libération, formant des nano-colonnes trans-synaptiques à l'état basal. Cette organisation précise à l’échelle nanométrique semble être un facteur clé dans l'efficacité de la transmission synaptique. Une autre avancée a été l'observation que les AMPARs diffusent à la surface des neurones et sont immobilisés à la synapse pour participer à la transmission synaptique. L'échange dynamique entre le pool diffusif d’AMPARs et les récepteurs immobilisés dans les nanodomaines participe au maintien de l’efficacité de la réponse synaptique lors de stimulations à hautes fréquences. L'objectif de ma thèse a été de déterminer le rôle des paramètres indiqués ci-dessus sur les propriétés de la transmission synaptique, à l'état basal et au cours de phénomènes dits de plasticité synaptique. Tout d'abord, nous avons identifié le rôle crucial de la Neuroligine dans l'alignement des nanodomaines d’AMPARs avec les sites de libération du glutamate. En plus de cela, nous avons mis en évidence l’impact de cet alignement sur l’efficacité de la transmission synaptique en perturbant celui-ci. En parallèle, nous avons démontré que les AMPARs désensibilisés sont plus mobiles à la membrane plasmatique que les récepteurs ouverts ou fermés, et ce, en raison d'une diminution de leur affinité pour les sites d’immobilisation synaptiques. Nous avons montré que ce mécanisme permettait aux synapses de récupérer plus rapidement de la désensibilisation et d'assurer la fidélité de la transmission synaptique lors de stimulations à hautes fréquences. Enfin, les synapses peuvent moduler leurs intensités de réponse grâce à des mécanismes de plasticité synaptique à long terme, et plus particulièrement, la dépression à long terme (LTD) qui correspond à un affaiblissement durable de ce poids synaptique. [...] À la suite des découvertes précédentes concernant le rôle de la nano-organisation dynamique des AMPARs pour réguler le poids et la fiabilité de la transmission synaptique, j'ai décidé d'étudier leur rôle dans l'affaiblissement et la sélection des synapses. J'ai découvert que la quantité d’AMPAR par nanodomaine diminue rapidement et durablement. Cette première phase semble due à une augmentation de l’internalisation des AMPARs. Dans un deuxième temps, la mobilité des AMPARs augmente suite à une réorganisation moléculaire de la synapse. Ce changement de mobilité des AMPARs permet aux synapses déprimées de maintenir leur capacité à répondre aux signaux neuronaux à hautes fréquences. Ainsi, nous proposons que l'augmentation de la mobilité des AMPARs au cours de la LTD permet de transmettre une réponse fidèle dans les synapses stimulées à hautes fréquences et donc de sélectivement les maintenir tout en éliminant les synapses inactivesThe brain is a complex network of interconnected neurons responsible for all our cognitive functions and behaviors. Neurons receive inputs at specialized contact zones named synapses which convert an all or none electrical signal to a chemical one, through the release of neurotransmitters. This chemical signal is then turned back in a tunable electrical signal by receptors to neurotransmitters. However, a single neuron receives thousands of inputs coming from several neurons in a spatial- and temporal-dependent manner. The precise mechanism by which neurons receive, integrate and transmit this synaptic inputs is highly complex and is still not perfectly understood. At excitatory synapses, AMPA receptors (AMPARs) are responsible for the fast synaptic transmission. With the recent developments in super-resolution microscopy, the community has changed its vision of synaptic transmission. One breakthrough was the discovery that AMPARs are not randomly distributed at synapses but are organized in nanodomains of ~80 nm of diameter containing ~20 receptors. This content is an important factor since it will determine the intensity of the synaptic response. Due to their mM affinity for glutamate, AMPARs can only be activated when located in an area of ~150 nm in front of the neurotransmitter release site. Recently, AMPAR nanodomains have been shown to be located in front of glutamate release sites and to form trans-synaptic nanocolumns at basal state. Thus, the nanoscale organization of AMPARs regarding release sites seems to be a key parameter for the efficiency of synaptic transmission. Another breakthrough in the field was the observation that AMPARs diffuse at the cell surface and are immobilized at synapses to participate to synaptic transmission. The dynamic exchange between AMPAR diffusive pool and the receptors immobilized into the nanodomains participates to maintain the efficiency of synaptic response upon high-frequency stimulation.The overall aim of my PhD has been to determine the role of each above listed parameters on the intimate properties of synaptic transmission both at basal state and during synaptic plasticity. First, we identified the crucial role of Neuroligin in the alignment of AMPAR nanodomains with glutamate release sites. In addition, we managed to break this alignment to understand its impact on synaptic transmission properties. In parallel, we demonstrated that, due to a decrease in their affinity for synaptic traps, desensitized AMPARs diffuse more at the plasma membrane than opened or closed receptors. This mechanism allows synapses to recover faster from desensitization and ensure the fidelity of synaptic transmission upon high-frequency release of glutamate. Finally, synapses can modulate their strength through long-term synaptic plasticity, in particular, Long-Term Depression (LTD) corresponds to a long-lasting weakening of synaptic strength and is thought to be important in some cognitive processes and behavioral flexibility through synapse selective elimination. Following the previous discoveries about the impact of AMPAR dynamic nano-organization at synapses on the regulation of the synaptic transmission strength and reliability, I decided to investigate their role in the weakening of synapses. I found that AMPAR nanodomain content drops down rapidly and this depletion last several minutes to hours. The initial phase seems due to an increase of endocytosis events, but in a second phase, AMPAR mobility is increased following a reorganization of the post-synaptic density. This change in mobility allows depressed synapses to maintain their capacity to answer to high-frequency inputs. Thus, we propose that LTD-induced increase in AMPAR mobility allows to conduct a reliable response in synapses under high-frequency stimulation and thus to selectively maintain them while eliminating the inactive ones
17
Pickard, Lisa Andrea. "Changes in the cell surface-distribution of ionotrophic glutamate receptors during development, receptor trafficking and synaptic plasticity in cultured hippocampal neurons." Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364872.
Full text
18
Soyez, Thomas. "Étude du glissement des dislocations dans le zirconium." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASP053.
Full textAbstract:
Les alliages de zirconium sont utilisés dans l’industrie nucléaire pour la fabrication des assemblages combustibles (tube guides, gaines et grilles). Afin de correctement prédire le comportement de ces alliages au cours de leur utilisation, il est nécessaire de connaître leur comportement mécanique. La déformation des métaux s’effectue généralement par glissement des dislocations et par maclage. Le zirconium présentant une structure hexagonale compacte, le développement de la déformation plastique est anisotrope. Pour une sollicitation suivant la direction du cristal, le mode de déformation principal correspondant au glissement de dislocations de vecteur de Burgers ne permet pas d’accommoder la déformation et le glissement de dislocations à vecteur de Burgers ou le maclage doit s’activer. Cette thèse a pour but d’étudier les propriétés de ces dislocations en se basant sur deux approches complémentaires, des observations en microscopie électronique à transmission (MET) et des simulations atomiques.Les observations MET ont permis de mettre en évidence le système de glissement des dislocations : ces dernières ne glissent que dans des plans pyramidaux de première espèce. Le glissement dévié est fréquemment observé entre plans pyramidaux de première espèce. Les dislocations apparaissent rectilignes et orientées préférentiellement dans leur orientation , soit l’intersection entre le plan de glissement et le plan de base. Lors d’essais de traction in situ en MET, le glissement de ces dislocations a été observé et un glissement plus difficile de la dislocation dans son orientation a été démontré. Deux types de glissement ont été observés : un glissement rigide où la dislocation avance en bloc dans son plan de glissement et un glissement visqueux des segments conduisant à la création de macro décrochements.Les simulations atomiques ont permis d’expliquer le glissement dans le plan pyramidal de première espèce via une étude des fautes d’empilement dans les plans possibles de glissement et via la détermination de la structure de cœur de la dislocation vis dans son état fondamental. Cette structure est pilotée par une dissociation en deux partielles non équivalentes dans le plan pyramidal de première espèce. L’étude de l’évolution de la structure de cœur dans son état fondamental sous une contrainte appliquée met en évidence une contrainte de Peierls différente en fonction du sens de la contrainte et démontre un glissement difficile de la dislocation avec une contrainte de Peierls trente fois plus élevée que celle nécessaire pour le glissement de la dislocation . L’activation thermique est donc nécessaire pour permettre à la dislocation vis d’avancer. En température, un glissement par germination de double décrochements a été observé dans des simulations de dynamique moléculaire et a été décrit par une loi thermiquement activée. La dislocation alignée dans une direction présente, quant à elle, une structure non planaire, se dissociant dans son plan de glissement pyramidal, mais également dans un second plan. La nature de ce second plan de dissociation, basal ou prismatique, varie avec le modèle énergétique choisiZirconium alloys are used in the nuclear industry as fuel cladding tubes and structural components of the fuel assemblies. In order to properly predict the mechanical behavior of those alloys throughout their usage time, it is necessary to understand the physical mechanisms controlling plasticity. Deformation in metals is usually accommodated by dislocation glide and twinning. Zirconium has a hexagonal close packed structure and its plastic deformation is anisotropic. For a mechanical loading along the axis of the crystal, the principal deformation mode corresponding to dislocation glide cannot accommodate the deformation and dislocation glide and twinning have to be activated. This thesis aims to study properties of dislocations based on two complementary approaches, Transmission Electron Microscopy (TEM) observations and atomic simulations.TEM observations underlined the glide system of the dislocations, which exclusively glide in first order pyramidal planes even, with cross slip between different first order pyramidal planes being activated at room temperature. dislocations appear rectilinear, with a preferential orientation along the direction which is the intersection between the glide plane and the basal plane. TEM in situ tensile test experiments show that this orientation glide with difficulty. Two types of glide mechanism were observed: a rigid motion where the dislocation keeps its shape while gliding and a viscous motion of these segments leading to the creation of macro-kinks.Atomic simulations rationalize the glide of dislocations in first order pyramidal plane with the existence of stacking faults in the possible glide planes and with a ground state structure of the screw dislocation which dissociates in two non-equivalent partial dislocations in a first order pyramidal plane. The evolution of this structure under an applied stress allowed to obtain the Peierls stress which depends on the direction of the applied stress and underlined a difficult glide: the Peierls stress of this screw dislocation is thirty times greater than the one of the dislocation. Thermal activation appears therefore necessary for dislocation glide. Molecular dynamics simulations evidence a glide of the screw dislocation operating by double kinks nucleation. The structure of the dislocation oriented in its direction is dissociated in its glide plane, i.e. a first order pyramidal plane, and also a secondary plane whose nature varies with the energetic model. This secondary dissociation is expected to explain the difficult glide of this orientation
19
Lester, R. A. J. "The involvement of excitory amino acid receptors in synaptic transmission and plasticity in area CA1 of the rat hippocampal slice." Thesis, University of Bristol, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379658.
Full text
20
Khlghatyan, Jivan, and Jivan Khlghatyan. "Regulation of glutamatergic neurotransmission, synaptic plasticity, sleep and behavior by D2-GSK3B-FXR1." Doctoral thesis, Université Laval, 2020. http://hdl.handle.net/20.500.11794/38090.
Full textAbstract:
Les études GWAS associent les variantes du gène Fxr1 à la schizophrénie, les maladies bipolaires, l’insomnie et la durée du sommeil. Gsk3β peut directement phosphoryler et ainsi réguler négativement Fxr1. De plus, les interactions fonctionnelles entre Gsk3β et Fxr1 sont associées avec la stabilité émotionnelle chez les humains. Comment Gsk3β-Fxr1 régule l’activité neuronale, la plasticité et le comportement reste inconnu. Gsk3β peut être activé en aval des récepteurs D2 de dopamine. L’activité de Gsk3β peut être modulée par les stabilisateurs d’humeur, les antipsychotiques et les antidépresseurs en régulant des comportements. Néanmoins, les corrélations neuroanatomiques de Gsk3β en aval des récepteurs D2 restent inexplorées. Nous avons étudié, en premier lieu, les relations de Gsk3β-Fxr1 avec l’activité neuronale et les comportements. Nous avons découvert que Fxr1 et son régulateur négatif Gsk3β affectent les comportements liés à l’anxiété ainsi que la neurotransmission glutamatergique via la régulation des récepteurs AMPA synaptiques. Deuxièmement, nous avons exploré l’Implication de Gsk3β-Fxr1 dans la plasticité synaptique et le sommeil. Nous avons constaté que Fxr1 est le régulateur central («maître») de la mise à l’échelle synaptique homéostatique. D’ailleurs, il est aussi engage dans l’homéostasie du sommeil et module la force synaptique en régulant les transcripts impliqués dans la synthèse locale des protéines et la structure synaptique. Troisièmement, dans le but de comprendre les corrélations neuroanatomiques nous avons généré une carte des neurones exprimant des récepteurs D2 de tout le cortex et leurs projections. En quatrième lieu, nous avons visé d’investiguer les fonctions de Gsk3β en aval des récepteurs D2 dépendamment de leur emplacement anatomique. L’invalidation (knockout) intersectoriel de Gsk3β dans les neurones D2 du cortex préfrontal murin par CRISPR/Cas9 nous a permis de révéler sa contribution dans la régulation des comportements cognitifs, sociaux et de ceux associés à l’humeur. En résumé, cette thèse de doctorat élucide les fonctions de Fxr1 dans le cerveau tout en démontrant l’utilité du CRISPR/Cas9 dans le ciblage génétique ayant pour but d’explorer les fonctions des gènes spécifiquement dans un circuit donné.Les études GWAS associent les variantes du gène Fxr1 à la schizophrénie, les maladies bipolaires, l’insomnie et la durée du sommeil. Gsk3β peut directement phosphoryler et ainsi réguler négativement Fxr1. De plus, les interactions fonctionnelles entre Gsk3β et Fxr1 sont associées avec la stabilité émotionnelle chez les humains. Comment Gsk3β-Fxr1 régule l’activité neuronale, la plasticité et le comportement reste inconnu. Gsk3β peut être activé en aval des récepteurs D2 de dopamine. L’activité de Gsk3β peut être modulée par les stabilisateurs d’humeur, les antipsychotiques et les antidépresseurs en régulant des comportements. Néanmoins, les corrélations neuroanatomiques de Gsk3β en aval des récepteurs D2 restent inexplorées. Nous avons étudié, en premier lieu, les relations de Gsk3β-Fxr1 avec l’activité neuronale et les comportements. Nous avons découvert que Fxr1 et son régulateur négatif Gsk3β affectent les comportements liés à l’anxiété ainsi que la neurotransmission glutamatergique via la régulation des récepteurs AMPA synaptiques. Deuxièmement, nous avons exploré l’Implication de Gsk3β-Fxr1 dans la plasticité synaptique et le sommeil. Nous avons constaté que Fxr1 est le régulateur central («maître») de la mise à l’échelle synaptique homéostatique. D’ailleurs, il est aussi engage dans l’homéostasie du sommeil et module la force synaptique en régulant les transcripts impliqués dans la synthèse locale des protéines et la structure synaptique. Troisièmement, dans le but de comprendre les corrélations neuroanatomiques nous avons généré une carte des neurones exprimant des récepteurs D2 de tout le cortex et leurs projections. En quatrième lieu, nous avons visé d’investiguer les fonctions de Gsk3β en aval des récepteurs D2 dépendamment de leur emplacement anatomique. L’invalidation (knockout) intersectoriel de Gsk3β dans les neurones D2 du cortex préfrontal murin par CRISPR/Cas9 nous a permis de révéler sa contribution dans la régulation des comportements cognitifs, sociaux et de ceux associés à l’humeur. En résumé, cette thèse de doctorat élucide les fonctions de Fxr1 dans le cerveau tout en démontrant l’utilité du CRISPR/Cas9 dans le ciblage génétique ayant pour but d’explorer les fonctions des gènes spécifiquement dans un circuit donné.
Variants in Fxr1 gene are GWAS-associated to schizophrenia, bipolar disorders, insomnia, and sleep duration. Gsk3β can directly phosphorylate and negatively regulate Fxr1. Moreover, functional interaction between Gsk3β and Fxr1 is associated with emotional stability in humans. How Gsk3β-Fxr1 regulates neuronal activity, plasticity and behaviors remains unclear. Gsk3β can be activated downstream of dopamine D2 receptors. Gsk3β activity can be modulated by mood stabilizers, antipsychotics and antidepressants to regulate behaviors. Nevertheless, neuroanatomical correlates of Gsk3β functions downstream of D2 receptors remain elusive. First, we investigated the relationship of Gsk3β-Fxr1 to neuronal activity and behaviors. We discovered that Fxr1 and its negative regulator Gsk3β affect anxiety-related behaviors and glutamatergic neurotransmission via regulation of synaptic AMPA receptors. Second, we addressed the involvement of Gsk3β-Fxr1 in synaptic plasticity and sleep. We discovered that Fxr1 is a master regulator of homeostatic synaptic scaling. Moreover, it is engaged during sleep homeostasis to modulate synaptic strength via regulation of transcripts involved in local protein synthesis and synaptic structure. Third, to understand neuroanatomical correlates of D2 receptor signaling we generated a cortex-wide map of D2 expressing neurons and their projection targets. Fourth, we aimed to understand anatomically defined functions of Gsk3β downstream of D2 receptors. CRISPR/Cas9 mediated intersectional knockout of Gsk3β in D2 neurons of mPFC elucidated its contribution to the regulation of cognitive, social and mood-related behaviors. Overall, this thesis sheds light on brain functions of a GWAS-identified risk gene Fxr1 and shows the utility of intersectional CRISPR/Cas9 mediated genetic targeting for the interrogation of circuitspecific functions of genes.
Variants in Fxr1 gene are GWAS-associated to schizophrenia, bipolar disorders, insomnia, and sleep duration. Gsk3β can directly phosphorylate and negatively regulate Fxr1. Moreover, functional interaction between Gsk3β and Fxr1 is associated with emotional stability in humans. How Gsk3β-Fxr1 regulates neuronal activity, plasticity and behaviors remains unclear. Gsk3β can be activated downstream of dopamine D2 receptors. Gsk3β activity can be modulated by mood stabilizers, antipsychotics and antidepressants to regulate behaviors. Nevertheless, neuroanatomical correlates of Gsk3β functions downstream of D2 receptors remain elusive. First, we investigated the relationship of Gsk3β-Fxr1 to neuronal activity and behaviors. We discovered that Fxr1 and its negative regulator Gsk3β affect anxiety-related behaviors and glutamatergic neurotransmission via regulation of synaptic AMPA receptors. Second, we addressed the involvement of Gsk3β-Fxr1 in synaptic plasticity and sleep. We discovered that Fxr1 is a master regulator of homeostatic synaptic scaling. Moreover, it is engaged during sleep homeostasis to modulate synaptic strength via regulation of transcripts involved in local protein synthesis and synaptic structure. Third, to understand neuroanatomical correlates of D2 receptor signaling we generated a cortex-wide map of D2 expressing neurons and their projection targets. Fourth, we aimed to understand anatomically defined functions of Gsk3β downstream of D2 receptors. CRISPR/Cas9 mediated intersectional knockout of Gsk3β in D2 neurons of mPFC elucidated its contribution to the regulation of cognitive, social and mood-related behaviors. Overall, this thesis sheds light on brain functions of a GWAS-identified risk gene Fxr1 and shows the utility of intersectional CRISPR/Cas9 mediated genetic targeting for the interrogation of circuitspecific functions of genes.
21
Kourdougli, Nazim. "Hippocampal structural reactive plasticity in a rat model of temporal lobe epilepsy : chloride homeostasis as a keystone." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM4091.
Full textAbstract:
Cette thèse a pour objectif spécifique d’explorer les événements précoces pouvant être à l’origine du bourgeonnement aberrant des fibres moussues (FM) du gyrus denté, une réorganisation majeure dans l’Epilepsie du Lobe Tempora (ELT). Nous avons utilisé le modèle pilocarpine d’ELT chez le rat afin de montrer que la transmission GABAergique jouait un rôle prépondérant dans la formation des FM aberrantes au cours de l’épileptogenèse. Ceci étant due à une altération de l’homéostasie chlore, suite à une augmentation de l’expression du co-transporteur NKCC1 et une diminution du co-transporteur KCC2. Nos résultats ont démontré que le récepteur aux neurotrophines p75NTR était un médiateur de l’action trophique de la réponse GABAergique dépolarisante sur le bourgeonnement aberrant des FM. Le blocage de l’action dépolarisante de la transmission GABAergique via l’utilisation de la bumétanide, a permis de réduire le bourgeonnement aberrant des MF en réduisant l’expression de p75NTR. Enfin, l’application transitoire de la bumétanide au cours de l’épileptogenèse a abouti à la réduction du nombre de crises récurrentes et spontanées au cours de la phase chronique d’ELT chez le rat. Ce travail a permis de dévoiler les mécanismes moléculaires sous-jacents de la réorganisation du réseau neuronal glutamatergique consécutif à une crise inaugurale dans un modèle d’ELT. Dans l'ensemble, cette thèse apporte un éclairage nouveau sur l’importance de l’interaction de la signalisation GABAergique avec les neurotrophines afin d’orchestrer la plasticité réactive au sein de l’hippocampe dans TLEThe present dissertation undertakes to investigate the early triggering events of the mossy fiber sprouting (MFS) in the dentate gyrus, a hallmark of hippocampal reactive plasticity in Temporal Lobe Epilepsy (TLE). We used the rat pilocarpine model of TLE to show that altered GABAA receptor-mediated transmission play a key role in the formation of early ectopic MFS during epileptogenesis. This is likely due to a compromised chloride homeostasis, as a result of increased expression of chloride loader NKCC1 and downregulation of the neuronal chloride extruder KCC2. We next addressed the mechanistic action of depolarizing GABAAR responses with regard to neurotrophin signaling. Our findings uncovered that the pan neurotrophin receptor p75 (p75NTR) mediated the sculpting action of depolarizing GABAAR responses on the ectopic MFS. Blockade of depolarizing GABAAR responses using the loop diuretic bumetanide reduced abnormal p75NTR subsequently decreased the ectopic MFS. Finally, transitory application of bumetanide during epileptogenesis resulted in reduction of spontaneous and recurrent seizures during the chronic phase of TLE. The rationale of this work is that unveiling the molecular mechanisms underlying the hippocampal post-seizure glutamatergic network rewiring will help to drive future novel therapeutic avenues involving chloride homeostasis and neurotrophin interplay. Overall, this dissertation shed a new light on how GABAergic transmission and neurotrophin signaling crosstalk can orchestrate reactive hippocampal plasticity in TLE
22
Coumis, Urania. "The role of galanin in synaptic transmission and plasticity in the CA1 area of the rodent hippocampus." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29073.
Full textAbstract:
Long-term potentiation (LTP) has been widely recognised as a model of the synaptic changes that may underlie learning and memory in vertebrates. It may be predicted that the physiological action of galanin at the cellular level would be to depress LTP, thereby causing an impairment in mnemonic processes mediated by the hippocampus. Experiments were designed to address three aspects of this hypothesis, namely (1) characterisation of the effect of galanin agonists and antagonists on synaptic transmission and plasticity in the CA1 area of rodent hippocampus and (2) investigation of glutamatergic synaptic plasticity in galanin knockout mice and their wild-type littermates. Exogenous galanin induced a does-dependent increase in the slope of baseline fEPSPs, which appeared to be dependent on the pathways from CA3 to CA1 being intact, but it did not have any effect on paired-pulse facilitation ratios. In CA3 hemisected hippocampal slices the aforementioned effect did not occur. The effect of galanin on LTP and long-term depression (LTD) of glutamate mediated synaptic transmission in apical and basal dendrites of CA1 pyramidal neurones were investigated using both intracellular and extracellular recording techniques in vitro. LTP induced in either apical or basal dendrites of CA1 pyramidal neurones by different paradigms was significantly inhibited by galanin. Galanin also inhibited LTP in hippocampal slices prepared form wild-type mice. This effect was reversible by the known galanin antagonist, galantide (M15). Galanin did not affect isolated pure NMDA receptor-mediated postsynaptic potentials or the loss of spike frequency adaptation and increase in input resistance evoked by metabotropic glutamate receptor activation indicating that its inhibition of LTP was downstream of these receptors. Galanin applied had no effect the expression of LTP indicating that galanin may inhibit LTP by interfering with kinase activity necessary for the induction of LTP e.g. protein kinase C. Galanin did not affect the induction of LTD. Subsequent studies in the galanin-null transgenic mice yielded no effect on synaptic strength or paired pulse facilitation ratios. Galanin seems to have inhibitory modulatory effect on excitatory neurotransmitters such as glutamate in the hippocampus, thereby delaying the neurodegenerative effect of age. The research described in this thesis is deemed of importance in biomedical research of drug therapy for protection against neurodegenerative disease.
23
Szulc, B. R. "Synthesis and discovery of the putative cognitive enhancer BRS-015 : effect on glutamatergic transmission and synaptic plasticity." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1462589/.
Full textAbstract:
This thesis is concerned with the discovery of a novel heterocyclic compound – BRS-015, its synthesis and an analysis of its effects on excitatory synaptic transmission at a major pathway in the brain. BRS-015 is related to the natural product clausenamide, which has been shown to facilitate synaptic transmission. As such, clausenamide and related analogues may possess therapeutic potential as memory enhancing drugs, which are in urgent need of development due to the increasing numbers of patients diagnosed with memory disorders and for which there is no current effective therapy. BRS-015 was synthesized using a novel approach to the core structure of clausenamide involving an intramolecular acylal cyclisation reaction, which has not previously been reported. The first section of the thesis opens with a description of the discovery, structure and biological activity of clausenamide and discussion of previous synthetic strategies adopted by a number of research groups and attempts to classify these into the varying approaches towards the central core of clausenamide. The second section describes the structure of the rat brain and the types of processes involved in memory formation, as well as the neurophysiological assays used to investigate synaptic transmission and plasticity. The second group of chapters describes our own approach to the core of clausenamide and the synthesis of BRS-015, with a detailed discussion of the structural analysis and investigation of the intramolecular acylal cyclisation reaction used during the synthetic process. The third chapter describes the neurophysiological assays used in our investigations into the effects of BRS-015, which was tested against glutamatergic synaptic transmission and plasticity in acute rat hippocampal slices. BRS-015 was shown to reversibly enhance the amplitude of AMPA receptor mediated EPSCs recorded from CA3 pyramidal neurones and evoked by dentate stimulation. When tested in the presence of selective glutamate receptor antagonists, BRS-015 did not have this powerful enhancing effect on kainate or NMDA receptor mediated EPSCs. In addition, BRS-015 increased the amplitude of glutamate-evoked currents in CA3 pyramidal neurones and did not alter short-term synaptic plasticity but facilitated the induction of mossy fibre LTP, with little effect at associational/commissural synapses. BRS-015 has striking enhancing properties on AMPA receptor mediated synaptic transmission at mossy fibre synapses either by directly interacting with AMPA receptors or via indirect modulation, the mechanisms of which could lead to synapse strengthening.
24
Jiang, Nan. "Plasticité de la transmission synaptique dans l’hippocampe et excitabilité intrinsèque dans un modèle murin de la maladie d’Alzheimer." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0137/document.
Full textAbstract:
La maladie d'Azheimer (MA) est une pathologie neurodégénérative qui est liée dans ses stades précoces à un dysfonctionnement synaptique et une perte de synapses. De nombreuses données cliniques obtenues chez des patients mais également des données expérimentales obtenues sur des modèles murins de la MA montrent qu'il existe un dimorphisme sexuel s'exprimant par un dépôt de plaques amyloïdes supérieur et une apparition précoce de troubles mnésiques chez les souris femelles par rapport aux souris mâles. Dans ce travail, nous avons étudié les altérations moléculaires et cellulaires de la MA ainsi que les déficits cognitifs associés chez la souris femelle APP/PS1, un modèle murin double transgénique de la MA. En parallèle nous avons étudié les altérations de la transmission et de la plasticité synaptique dans le stratum moleculare, une couche proche du gyrus dentelé (DG) en raison de la forte densité de plaques amyloïdes dans cette région de l'hippocampe.Nous avons mis en évidence la présence de nombreuses plaques amyloïdes dans le DG en quantité supérieure chez les femelles âgées de 6 mois par rapport aux mâles du même âge ainsi qu'une forte activation des cellules gliales astrocytes et microglie. Ces altérations moléculaires et cellulaires s'accompagnent de déficits mnésiques hippocampo-dépendants (test du comportement de peur conditionné et test de la nouvelle localisation spatiale d'un objet) dès l'âge de 4 mois chez les femelles alors que les mâles ne présentent aucun déficit jusqu'à l'âge de 12 mois.Nous avons alors étudié les propriétés électriques des neurones du gyrus dentelé (DG), la transmission et la plasticité de la synapse voie perforante - neurones du gyrus dentelé (synapse PP-DG) chez la souris femelle âgée de 6 mois en comparant les deux génotypes APP/PS1 vs sauvage.Les neurones du DG présentent deux populations distinctes en terme de résistance d'entrée et de patron de décharge de potentiels d'action (PAs). A l'inverse, le potentiel membranaire de repos, la résistance d'entrée, le seuil d'activation et l'amplitude du potentiel d'action ne sont pas modifiés chez la souris APP/PS1 vs la souris sauvage. La fréquence de décharge des potentiels d'action est augmentée chez la souris APP/PS1 sans que la probabilité de décharge en fonction de la pente du pied du potentiel d'action (courbe E-S) soit différente entre la souris APP/PS1 et la souris sauvage. La transmission basale à la synapse PP-DG est modifiée chez la souris APP/PS1 vs la souris sauvage sans altérations du ratio AMPA/NMDA ni de l'index de rectification AMPA. La fréquence des courants miniatures NMDA est augmentée dans les neurones DG de la souris APP/PS1 vs la souris sauvage ce qui suggère le démasquage de synapses silencieuses qui n'expriment peu ou pas de récepteurs AMPA. La potentialisation à long terme (PLT) de l'amplitude des potentiels d'action synchrone est diminuée d'environ 50% chez la souris APP/PS1. La diminution de la PLT observée chez la souris APP/PS1 est en partie liée à des altérations des propriétés intrinsèques des neurones du DG comme le montre le déplacement des courbes E-S induit par la PLT qui traduit une augmentation d'excitabilité de la souris APP/PS1.En conclusion nos résultats montrent un dimorphisme sexuel important avec un dépôt des plaques amyloïdes et une activation neuroinflammatoire des cellules gliales plus précoce chez la souris femelle vs mâle. En parallèle, des déficits importants de la mémoire hippocampale-dépendante sont observés ainsi que des altérations de la transmission et de la plasticité synaptique à la synapse voie perforante - neurones du gyrus dentelé, une synapse clé de l'intégration des informations mnésiques en provenance du cortex enthorhinalAzheimer's disease (AD) is a neurodegenerative disease that is linked in its early stage to synaptic dysfunction and loss of synapses. Numerous clinical data obtained from patients but also experimental data obtained on mouse models of AD show that there is a sexual dimorphism evidenced by a higher amyloid plaque deposition and an early onset of memory disorders in female mice compared to male mice.In this work, we investigated the molecular and cellular alterations of AD as well as the associated cognitive deficits in female APP/PS1 mice, a double transgenic murine model of AD. In parallel we studied the alterations of hippocampal synaptic transmission and plasticity in the stratum moleculare, a layer in the vicinity of the dentate gyrus (DG) which specifically displayed a high density of amyloid plaques. We showed the presence of numerous amyloid plaques in the DG in a larger amount in 6 month old females compared to age-matched males as well as a strong activation of astrocyte and microglia glial cells. These molecular and cellular alterations are accompanied by hippocampo-dependent memory deficits (contextual fear conditioning and novel object place recognition task) from the age of 4 months in females whereas males have no deficit until the age of 12 months. We then studied the electrical properties of DG neurons, the transmission and the plasticity of the perforant pathway - DG neurons (PP-DG synapse) in the 6-month old female mouse by comparing the two genotypes APP/PS1 vs wild type (WT).In both genotypes, DG neurons displayed two distinct populations in terms of input resistance and action potential discharge pattern (APs). In contrast, the resting membrane potential, the input resistance, the activation threshold and the amplitude PAs were not modified in APP/PS1 vs WT. The frequency of discharge of APs was increased in APP/PS1 without shift of E-S curve which relates EPSP-slopes to the associated AP firing probability.Basal transmission at the PP-DG synapse was altered in the APP/PS1 mouse vs WT without alterations in the AMPA/NMDA ratio or the AMPA rectification index. The frequency of the NMDA miniature currents was increased in APP/PS1 DG neurons vs WT which suggests the unmasking of silent synapses that express almost no AMPA receptors. The long term potentiation (LTP) of population spike amplitude was decreased by approximately 50% in APP/PS1 mice. The decrease in LTP observed in APP/PS1 was partly related to alterations in the intrinsic properties of DG neurons as evidenced by LTP-induced shifts of E-S curves, which reflects an increased excitability for APP/PS1 mice.In conclusion our results show a prominent sexual dimorphism with much earlier amyloid plaque deposition, neuroinflammatory glial activation in female vs male APP/PS1. In parallel, significant deficits in hippocampal-dependent memory are observed as well as alterations of synaptic transmission and plasticity at the PP-DG synapse, a key synapse of the integration of mnesic informations originated from the entorhinal cortex
25
Sibille, Jérémie. "Activity-dependent astroglial potassium and calcium signals contribute to hippocampal short-term plasticity." Paris 7, 2013. http://www.theses.fr/2013PA077284.
Full textAbstract:
I- Les astrocytes contribuent à la neurotransmission par une variété de mécanismes, allant de l'isolation de la synapse à la signalisation dynamique. Ces cellules ont une signalisation dynamique qui leur permet à la fois de détecter l'activité neuronale grâce à des canaux ioniques, des récepteurs ou des transporteurs aux différents neurotransmetteurs, et de répondre de manière appropriée par une signalisation calcique élaborée, par une plasticité morphologique ou bien par le relargage de nombreuses substances neuroactives. Cependant la nature, la plasticité, et l'impact des courants induits par l'activité neuronale sur la plasticité synaptique à court-terme est encore élusive dans les astrocytes de l'hippocampe. Nous avons montré qu'une stimulation unique des collatérales de Schaeffer dans des tranches d'hippocampe induit dans les astrocytes de stratum radiatum un courant entrant, complexe et prolongé, lui-même synchronisé à la transmission synaptique rapide des cellules pyramidales de la région CAl. Ce courant est constitué de trois composantes: un courant potassique lent, sous-tendu par les canaux Kir4. 1, un courant de transporteur au glutamate transitoire et un courant résiduel lent, partiellement sous-tendu par des transporteurs au GABA et d'autres canaux potassiques que le Kir4. 1. Tous les courants présentent une plasticité à court-termeactivité dépendante, cependant seul le courant astrocytaire de transporteur au glutamate présente une plasticité de type neuronale. Étant donné que 80% du courant astrocytaire évoqué synaptiquement est sous-tendu par les canaux potassiques de type Kir4. 1, nous avons investigué son effet sur la plasticité synaptique à court-terme de l'hippocampe, en combinant l'électrophysiologie à la modélisation mathématique. En utilisant la souris invalidée pour le gène Kir 4. 1 sélectivement dans les cellules gliales, nous avons trouvé que les canaux Kir4. 1 diminuent les réponses synaptiques aux stimulations répétitives ainsi que la potentialisation post-tétanique. Afin de d'identifier la voie de signalisation et la dynamique du cycle potassique entre les astrocytes et les neurones pendant l'activité neuronale, nous avons construit un modèle mathématique de trois compartiments qui quantifie les échanges de potassium entre les neurones, les cellules gliales et l'espace extracellulaire. Nous avons trouvé que les canaux Kir4. 1 sont responsables de la lente capture de potassium pendant l'activité neuronale, ce qui régule l'excitabilité neuronale dans des conditions tant physiologiques que pathologiques. Finalement, nous avons investigué la signalisation calcique activité-dépendante dans les astrocytes des régions CA1 et CA3 de l'hippocampe ainsi que son impact sur la transmission et la plasticité synaptique à court terme Nous avons trouvé que bien que de tels signaux régulent l'activité synaptique des synapses des collatérales de Schaeffer dans la région CA1, son effet n'est que modeste sur la synapse de la fibre moussue dans la région CA3. Cela est probablement dû à la différence de couverture astrocytaire des synapses dans ces deux régions de l'hippocampe, comme le suggère les études de microscopie électronique ainsi que le patron différentiel d'expression de la connexine 30, une protéine astrocytaire qui détermine la localisation synaptique des prolongements astrocytaires. De façon remarquable, la connexine 30 dans les astrocytes régule fortement la plasticité à court terme des synapses des fibres moussues dans la région CA3 de l'hippocampe, révélant ainsi le rôle important des astrocytes dans la régulation synaptique des niveaux de glutamate.
26
Wood, Catherine Louise. "The role of PICK1-Actin cytoskeleton interactions in synaptic transmission and plasticity at the hippocampal schaffer collateral synapse." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500399.
Full text
27
Lucas, Sarah Jane. "The role of group II metabotropic glutamate receptors in synaptic transmission and synaptic plasticity in the lateral amygdala." Thesis, University of Bristol, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.544343.
Full text
28
Cheng, Wenwen. "Amyloid-β oligomers reduces glutamatergic transmission and inhibits synaptic plasticity with underlying mechanisms suggestting akap150 modulates diverse synaptic functions." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/283407.
Full textAbstract:
Beta amiloide (Aß), es un péptido generado a partir de la proteína precursora de amiloide (APP) por las neuronas, que se cree esta implicado en la base de la fisiopatología de la enfermedad de Alzheimer (AD). Aß está directamente implicada en la modulación de la función sináptica y los niveles patológicos de Aß inhiben la plasticidad sináptica. Las formas solubles de A afectan negativamente al proceso de la transmisión sináptica, implicando la pérdida de los receptores sinápticos por mecanismos todavía desconocidos. Los principales receptores de glutamato ionotrópicos implicados en la transmisión sináptica excitatoria son los receptors para el ácido 4,5 alfa-amino-3-hidroxi-metil-isoxazolpropiónico (AMPARs) y los receptores de N-metil D-aspartato (NMDAR). El movimiento de los AMPARs dentro y fuera de la sinapsis, entre los depósitos intracelulares y la superficie de la célula juega un papel muy importante en los fenomenos de plasticidad sináptica como la potenciaón o la depression a largo término.
La proteína de anclaje para la quinasa A (AKAPs), juega un papel crítico en la plasticidad sináptica y en la estabilización de AMPARs y NMDAR. En nuestro estudio, la exposición de las neuronas corticales cultivadas a Aβo o NMDA (generandose depression a largo término) reduce los niveles de proteína AKAP150. Mediante el uso de diferentes agentes farmacológicos y herramientas moleculares, hemos estudiado los cambios en los niveles de AKAP provocados por Aβo y NMDA. Nuestros resultados indican una reducción de AKAP150 por estimulación de NMDAR y por Aßo. Este efecto es dependiente de la actividad clacineurina y del proteosoma. Por otra parte, el efecto reductor de Aβo y NMDA en los niveles de AMPAR fue imitado mediante el silenciamiento de la expresión de AKAP150 y bloqueado por la sobreexpresión de AKAP150.
Aβo podría estar implicado en el déficit de transporte dendrítico de los ARNm y su traducción. Los miRNAs son pequeños ARN no codificantes que actúan como reguladores post-transcripcional de la expresión génica. En AD temprana, que presenta neuritas distróficas y el fracaso sináptica, hay una alteración en los niveles de ciertos miRNAs. La exposición a largo plazo de Ao demostró que miR125a y miR132 fueron tanto reducen mientras que la exposición a largo plazo de NMDA induce la disminución de miR181a. Los experimentos con inhibidores indicaron que puede y Ca2+ pueden estar implicados en la modulación de mir181a por la exposición a largo plazo de NMDA.Beta amyloid (Aß) is a peptide generated from the amyloid precursor protein (APP) by the neurons, which is believed to be involved in the basis of the pathophysiology of Alzheimer's disease (AD). Aß is directly involved in modulating synaptic function and pathological Aß levels inhibit synaptic plasticity. Soluble forms of A adversely affect the process of synaptic transmission, involving the loss of synaptic receptors by yet unknown mechanisms. Major ionotropic glutamate receptors implicated in excitatory synaptic transmission are the receptors for the alpha 4,5-amino-3-hydroxy-methyl-isoxazolepropionic (AMPARs) receptors and N-methyl D-aspartate receptor (NMDAR). The movement of AMPARs into and out of the synapse between intracellular stores and the cell surface plays an important role in synaptic plasticity phenomena as long-term potentiation (LTP) or long-term depression (LTD). The A-kinase anchoring protein (AKAPs), plays a critical role in synaptic plasticity and in stabilizing NMDAR and AMPARs. In our study, exposure of cultured cortical neurons to Aβo or NMDA (cLTD) reduced the levels of protein AKAP150. By using different pharmacological agents and molecular tools, we studied the changes in the levels of AKAP induced Aβo and NMDA. Our results indicate that this effect is dependent on proteasome and calcineurin activities. Moreover, the reducing effect of NMDA on Aβo and AMPAR levels was mimicked by silencing expression AKAP150 and blocked by overexpression of AKAP150. Aβo could be involved in the deficit of dendritic mRNA transport and translation. miRNAs are small non-coding RNAs that act as post-transcriptional regulators of gene expression. In early AD, and dystrophic neurites having the synaptic failure, there is an alteration in the levels of certain miRNAs. Exposure to long-term showed Ao miR125a and miR132 were reduced as much exposure to NMDA induces long-term decline of miR181a. Inhibitor experiments indicated that Ca2 + can and may be involved in modulating mir181a by long term exposure to NMDA.
29
Klook, Kerstin Carina [Verfasser]. "Structural and functional determinants of synaptic transmission and plasticity at layer 4 synapses in the neocortex / Kerstin Carina Klook." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2012. http://d-nb.info/1023969718/34.
Full text
30
Willmes, Claudia Gisela [Verfasser]. "Investigation of hippocampal synaptic transmission and plasticity in mice deficient in the actin-binding protein Drebrin / Claudia Gisela Willmes." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1140487078/34.
Full text
31
Beauchemin-Turcotte, Marie-Eve. "Modulation of glutamatergic synaptic transmission and plasticity by sigma receptor type 1 in the CA1 region of the hippocampus." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27224.
Full textAbstract:
The sigma receptor (sigmaR), once considered a subtype of opioid receptor, is now described as a distinct pharmacological entity. sigma1Rs are thought to be implicated in neuropsychiatric disorders such as schizophrenia, depression as well as in learning and memory. The modulation of N-methyl-D-aspartate receptor (NMDAR) by the sigma1R has been extensively documented; however, the mechanism through which the sigma1R modulates the NMDAR has been a mystery for almost two decades. Here, I report that sigma1R activation increases NMDAR responses and long-term potentiation (LTP) by blocking a small conductance Ca2+-activated K+ current (SK channels) known to shunt NMDAR responses. Therefore, the blockage of SK channels and the resulting increased Ca2+ influx through the NMDAR enhances NMDAR responses and LTP. These results emphasize the importance of the sigma1R as a post-synaptic regulator of synaptic transmission.
32
真子, 北川, and Mako Kitagawa. "Developmental fine-tuning of excitatory synaptic transmission at input synapses in the rat inferior colliculus." Thesis, https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB13127446/?lang=0, 2020. https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB13127446/?lang=0.
Full textAbstract:
本研究では、聴覚神経系で入力の統合を担う下丘におけるシナプス伝達特性の生後発達段階における変化について、シナプス電流をパッチクランプ法で計測した。NMDA-EPSCにおいて、聴覚入力開始後に減衰時間が短縮していた。上行性経路からのシナプス伝達では、発達段階に応じて短期シナプス可塑性が変化した。一方で、交連性経路からのシナプス伝達では、発達段階に伴う短期シナプス可塑性の傾向には有意な変化はなかった。The inferior colliculus (IC) is the primal center of convergence and integration in the auditory pathway. I have measured excitatory synaptic currents (EPSCs) of the neurons in the central nucleus of the IC in response to stimulation of the lateral lemniscus and the commissure of the IC. Before hearing onset, the lemniscus inputs exhibited short-term depression, whereas commissural inputs showed facilitation. After hearing onset, the NMDA-EPSCs exhibited faster decay for both pathways. Furthermore, the EPSCs showed less short-term plasticity in both pathways. These developmental changes may ensure faster and more reliable signal transmission to the IC after onset of hearing.
博士(理学)
Doctor of Philosophy in Science
同志社大学
Doshisha University
33
Toland, Andrew Hamilton. "Short-Term Plasticity at the Schaffer Collateral: A New Model with Implications for Hippocampal Processing." PDXScholar, 2012. https://pdxscholar.library.pdx.edu/open_access_etds/756.
Full textAbstract:
A new mathematical model of short-term synaptic plasticity (STP) at the Schaffer collateral is introduced. Like other models of STP, the new model relates short-term synaptic plasticity to an interaction between facilitative and depressive dynamic influences. Unlike previous models, the new model successfully simulates facilitative and depressive dynamics within the framework of the synaptic vesicle cycle. The novelty of the model lies in the description of a competitive interaction between calcium-sensitive proteins for binding sites on the vesicle release machinery. By attributing specific molecular causes to observable presynaptic effects, the new model of STP can predict the effects of specific alterations to the presynaptic neurotransmitter release mechanism. This understanding will guide further experiments into presynaptic functionality, and may contribute insights into the development of pharmaceuticals that target illnesses manifesting aberrant synaptic dynamics, such as Fragile-X syndrome and schizophrenia. The new model of STP will also add realism to brain circuit models that simulate cognitive processes such as attention and memory. The hippocampal processing loop is an example of a brain circuit involved in memory formation. The hippocampus filters and organizes large amounts of spatio-temporal data in real time according to contextual significance. The role of synaptic dynamics in the hippocampal system is speculated to help keep the system close to a region of instability that increases encoding capacity and discriminating capability. In particular, synaptic dynamics at the Schaffer collateral are proposed to coordinate the output of the highly dynamic CA3 region of the hippocampus with the phase-code in the CA1 that modulates communication between the hippocampus and the neocortex.
34
Lepsveridze, Eka. "Synaptic transmission and plasticity in major excitatory hippocampal synapses of L1 conditional and CHL1 constitutive knockout mice (Mus musculus L., 1758)." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=980970547.
Full text
35
Kieselmann, Olga [Verfasser]. "Einfluss von Lysophosphatidsäure auf synaptische Transmission und Expressionsanalysen von Plasticity related gene 1 und LPA-Rezeptoren während der Gehirnentwicklung / Olga Kieselmann." Berlin : Freie Universität Berlin, 2011. http://d-nb.info/1025353811/34.
Full text
36
Xing, Xiaomin. "Genetic and functional analysis of synaptic CA²⁺ dynamics in Drosophila." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/2168.
Full textAbstract:
Ca²⁺ influx is one of the critical events that trigger synaptic vesicular release, and the accumulation of residual free Ca²⁺ in synapses is also important for activity-dependent synaptic plasticity. Ca²⁺ imaging with fluorescence indicators (synthetic or genetically encoded) is a powerful approach to monitor Ca²⁺ levels in neurons and synapses. Although accumulating studies in vertebrate systems have been carried out to demonstrate the role of Ca²⁺ in synaptic transmission and plasticity, most of these studies rely on pharmacological methods to infer the molecular mechanism, with less emphasis on forward genetic analysis. The Drosophila neuromuscular junction (NMJ) is a powerful neurogenetic platform for studying synaptic transmission, because of the availability of many mutations. However, not many mutations have been analyzed with Ca²⁺ imaging. Besides, although Genetically Encoded Ca²⁺ Indicators (GECIs) including GCaMPs are increasingly popular as the tool to identify neuronal circuits activated by certain stimuli or mediating particular behaviors, the physiological and functional interpretation of neuronal Ca²⁺ transients reported by GECIs remain obscure.
By expressing GCaMPs in NMJ synapses, I characterized a spectrum of genetic mutations including sodium channel alleles parats¹, parabss¹, potassium channel mutations Shaker (ShM, Sh¹²⁰), Shab³, ether-a-go-go (eag¹, eag⁴pm), and double mutant eag¹ Sh¹²⁰. Drosophila NMJs contain at least three different types of synapses, which include glutamatergic tonic motor synapse type Ib, phasic motor synapse type Is, and modulatory octopaminergic synapse type II. In this study, I found that the ion channel mutations did not uniformly alter the Ca²⁺ dynamics in type Ib, Is and II synapses. Based on genetic dissection and pharmacological analyses, I concluded that the excitability type I and type II synapses are differentially regulated by various ion channels, and that ion channels mainly influence the influx of Ca²⁺ upon membrane depolarization but not the subsequent clearance.
I also attempted to interpret the significance of synaptic Ca²⁺ transients by correlating Ca²⁺ imaging with electrophysiological recordings. One important gap in the application of GCaMP indicators is its postsynaptic physiological relevance. Correlation of synaptic GCaMP Ca²⁺ transients with postsynaptic currents simultaneously recorded by focal extracellular recording indicated that Ca²⁺ transients reported by GCaMPs were slow, and did not reflect immediate synaptic transmission. Rather, the kinetics of synaptic Ca²⁺ transients was temporally correlated with short-term synaptic plasticity such as facilitation and depression. The hyperexcitable ion channel mutations Sh and parabss¹ enhanced the synaptic Ca²⁺ transient amplitudes as well as depression. Type Is synapses of hyperexcitable mutations such as eag¹ Sh¹²⁰ and parabss¹ often displayed single stimulus pulse-evoked Ca²⁺ transients, which were induced by high frequency repetitive firing of action potentials. Such Ca²⁺ transients were correlated with supernumerary peaks of postsynaptic currents. Based on the slow kinetics and the correlation with short-term plasticity, I conclude that GCaMP Ca²⁺ signals better reflect the accumulation of cytosolic residual Ca²⁺. The spontaneous Ca²⁺ waves in larval motor neurons were well correlated with high frequency nerve action potentials, suggesting that accumulation of residual Ca²⁺ occurs in larval crawling.
Overall, this study provided important information about the different excitability control and Ca²⁺ clearance mechanisms in different synapses, and examined how membrane excitability controls the influx and accumulation of synaptic cytosolic residual Ca2+, as indicated by GCaMPs. Further, by correlating synaptic Ca²⁺ dynamics with electrophysiology, this study also investigated how to interpret GCaMP Ca²⁺ signals in the context of facilitation and depression, establishing a basis for an integrated approach of studying short-term synaptic plasticity from complementary physiological signals.
37
Malinina, Evgenya. "Neurotransmission and functional synaptic plasticity in the rat medial preoptic nucleus." Doctoral thesis, Umeå : Umeå university, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-25874.
Full text
38
Warren-Paquin, Maude. "Regulation of synaptic plasticity at the Drosophila larval NMJ : the role of the small GTPase Rac." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112319.
Full textAbstract:
We are interested in understanding the molecular mechanisms that govern synaptic growth and plasticity. Recent evidence from several laboratories suggests that small GTPases play an important role in the promotion of neurite outgrowth; however, their role in the control of synaptic growth and functional plasticity is not well understood. The goal of this thesis is to investigate the role of small GTPases (including Rac, Rho and Cdc42) in the regulation of synaptic growth in vivo, using the Drosophila larval neuromuscular junction (NMJ) synapses as a model system. Our results show that presynaptic overexpression of Rac, but not of Rho or Cdc42, positively regulates both synaptic structure and function. Genetic loss of Rac leads to embryonic lethality, making it impossible to assess the full loss-of-function phenotype using conventional mutants. To circumvent this, we use the MARCM (Mosaic Analysis with a Repressible Cell Marker) technique to generate single motor neuron clones devoid of all genetic copies of Rac. Our data suggest that Rac activity is crucial for normal synaptic development. In support of this conclusion, we demonstrate that genetic removal of trio, a guanine nucleotide exchange factor (GEF) that is known to activate Rac, leads to a drastic reduction in the number of synaptic boutons. In addition, genetic removal of one copy of trio is sufficient to suppress the gain-of-function phenotype of Rac. Moreover, we demonstrate that partial removal of the fragile X mental retardation gene (dfmr1), a known suppressor of Rac, enhances the gain-of-function phenotype of Rac. Taken together, our findings support a model in which Rac signaling positively regulates synaptic growth and function at the Drosophila larval NMJ.
39
Bushell, Trevor John. "The role of group II and group III metabotropic glutamate receptors in synaptic transmission and plasticity in the mouse and rat hippocampus." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337226.
Full text
40
Ganguly, Archan. "The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning." Ohio University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1331263683.
Full text
41
Diana, Marco Alberto. "Charakterisierung von einer retrograden Modulation inhibitorischer synaptischer Transmission im Kleinhirn der Ratte." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=971021988.
Full text
42
McCaffery, Brian. "Studies of the roles of metabotropic glutamate receptors in synaptic transmission and plasticity in the perirhinal and hippocampal cortices of mice and rats." Thesis, University of Bristol, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300562.
Full text
43
Berthoux, Coralie. "Rôle des récepteurs 5-HT2A et 5-HT6 du cortex préfrontal dans la modulation de la transmission synaptique, la plasticité et la cognition." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT166.
Full textAbstract:
La sérotonine est impliquée dans de nombreuses fonctions physiologiques comme la régulation de l’appétit, du sommeil, de la douleur, de l’humeur et de la cognition. Elle agit par l’intermédiaire de différents récepteurs dont la plupart sont couplés aux protéines G. Parmi ceux-ci, les récepteurs 5-HT2A et 5-HT6 suscitent un intérêt particulier car ils sont la cible de nombreux agents thérapeutiques, comme les antidépresseurs et les antipsychotiques de dernière génération. Ces molécules administrées pour traiter la schizophrénie ont des effets bénéfiques sur les symptômes positifs (hallucinations, délires) et négatifs (manque de motivation). Cependant, ils n’ont que peu d’effets sur les déficits cognitifs (troubles de la mémoire de travail, de l’attention, asociabilité) qui compromettent l'intégration sociale et professionnelle des patients ainsi que leur qualité de vie. Ces déficits sont en grande partie retrouvés chez les consommateurs chroniques de cannabis durant l’adolescence suggérant des mécanismes pathologiques communs. La découverte de nouvelles stratégies thérapeutiques pour traiter ces déficits cognitifs constitue donc un enjeu de santé publique majeur.Au cours de mon travail de thèse, j’ai étudié le rôle des récepteurs de la sérotonine, en me focalisant sur les récepteurs 5-HT2A et 5-HT6, dans la modulation de la transmission et la plasticité synaptique au niveau du cortex préfrontal. En combinant des approches biochimiques à des analyses électrophysiologiques et comportementales, j’ai dans un premier temps démontré l'implication des récepteurs 5-HT2A exprimés au niveau des synapses thalamocorticales dans l’induction de la plasticité synaptique et dans la mémoire associative. Dans un deuxième temps, j’ai déterminé les bénéfices du blocage précoce des récepteurs 5-HT6 sur les déficits cognitifs induits dans un modèle neurodéveloppemental de schizophrénie et un modèle de consommation chronique de cannabis durant l’adolescence. Cette étude permet ainsi d’envisager de nouvelles stratégies thérapeutiques pour prévenir l’apparition des déficits cognitifs observés dans les maladies psychiatriques, notamment chez les sujets à risqueSerotonin is involved in many physiological functions, such as the control of appetite, sleep, pain, mood and cognition. This major neuromodulator acts via different receptors, which are, for the most part, coupled to G-proteins. Among these, 5-HT2A and 5-HT6 receptors are of particular interest since they are the target of many therapeutic drugs, such as antidepressants and last-generation antipsychotics. These are administered to treat schizophrenia and have beneficial effects on positive (hallucinations, delusions) and negative (lack of motivation) symptoms. Nevertheless, they poorly control cognitive deficits (impaired working memory, decreased attention, alteration in social cognition) which severely compromise the social integration of patients and their quality of life. These deficits are also found in chronic cannabis users during adolescence, suggesting common pathological mechanisms. Therefore, the discovery of new therapeutic strategies to treat these cognitive deficits is a major public health issue.During my thesis work, I studied the role of serotonin receptors, focusing on 5-HT2A and 5-HT6 receptors, in the modulation of synaptic transmission and plasticity in the prefrontal cortex. By combining biochemical approaches with electrophysiological and behavioral analyses, I initially demonstrated that 5-HT2A receptors expressed at thalamocortical synapses play a crucial role in the induction of synaptic plasticity and in associative memory. Secondly, I demonstrated the benefits of early blockade of 5-HT6 receptors for preventing cognitive deficits induced in a neurodevelopmental model of schizophrenia and a model of chronic cannabis abuse during adolescence. These studies offer new therapeutic strategies to prevent the emergence of cognitive deficits and conversion to schizophrenia in at-risk subjects
44
Carter, Lucy Mary. "Evolutionary ecology of reproductive strategies in malaria parasites." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9910.
Full textAbstract:
For vector-borne parasites such as malaria, how within- and between-host processes interact to shape transmission is poorly understood. In the host, malaria parasites replicate asexually but for transmission via mosquitoes to occur, specialized sexual stages (gametocytes) must be produced. Once inside the mosquito vector, gametocytes immediately differentiate into male and female gametes, and motile male gametes must swim through the hostile environment of the bloodmeal to find and fertilise female gametes. Despite the central role that gametocytes play in disease transmission, explanations of why parasites adjust gametocyte production in response to in-host factors remain controversial. Furthermore, surprisingly little is known about the mating behaviour of malaria parasites once inside the mosquito. Developing drugs and/or vaccines that prevent transmission by disrupting sexual stages are major goals of biomedicine, but understanding variation in gametocyte investment and male gamete behaviour is key to the success of any intervention. First, I propose that the evolutionary theory developed to explain variation in reproductive effort in multicellular organisms provides a framework to understand gametocyte investment strategies in malaria parasites. I then demonstrate that parasites appear to change their reproductive strategies in response to environmental cues and in a manner consistent with our predictions. Next, I show how digital holographic microscopy can be used to characterise the morphology and motility of male gametes. I then provide evidence for non-random movement of male gametes and that gamete interactions with red blood cells appear to hinder mating success in a bloodmeal. Finally, I discuss the variation in gametocyte differentiation and fertilisation success when exposed to a number of factors implicated in gametocyte activation. The data presented here provides important information on the basic biology of malaria parasite reproductive stages and demonstrates considerable variation in parasite traits and behaviours in response environmental changes; both in the host and in the mosquito vector.
45
Hara, Yuko. "Dopamine-dependent plasticity and subcellular locations of dopamine D1 receptors : in relation to glutamate NMDA receptors and endogenous opioids in the nucleus accumbens, implications for schizophrenia /." Access full-text from WCMC, 2008. http://proquest.umi.com/pqdweb?did=1528441261&sid=22&Fmt=2&clientId=8424&RQT=309&VName=PQD.
Full text
46
Koon, Alex C. "Autoregulatory and Paracrine Control of Synaptic and Behavioral Plasticity by Dual Modes of Octopaminergic Signaling: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/572.
Full textAbstract:
Synaptic plasticity—the ability of a synapse to change—is fundamental to basic brain function and behavioral adaptation. Studying the mechanisms of synaptic plasticity benefits our understanding of the formation of neuronal connections and circuitry, which has great implications in the field of learning and memory and the studies of numerous human diseases.
The Drosophila larval neuromuscular junction (NMJ) system is a powerful system for studying synaptic plasticity. The NMJ consists of at least two different types of motorneurons innervating the body wall muscles. Type I motorneurons controls muscle contraction using glutamate as the neurotransmitter, while type II are modulatory neurons that contain octopamine. Octopamine is a potent modulator of behavior in invertebrates. Nevertheless, its function at the synapse is poorly understood.
In my thesis research, I investigated the role of octopamine in synaptic plasticity using the Drosophila NMJ system. Preliminary observations indicate that increased larval locomotion during starvation results in an increase of filopodia-like structures at type II terminals. These structures, which we termed as “synaptopods” in our previous studies, contain synaptic proteins and can mature into type II synapses. I demonstrated that this outgrowth of type II terminals is dependent on activity and octopamine. Mutations and genetic manipulations affecting the production of octopamine decrease synaptopods, whereas increase of type II activity or exogenous application of octopamine increase synaptopods. Interestingly, I found that the type II octopaminergic neurons have an absolute dependence on activity for their innervation of the muscles. Blocking activity in these neurons throughout development results in no type II synapses at the NMJ, whereas blocking activity after the formation of synapses results in gradual degradation of type II terminals.
Next, I examined the autoregulatory mechanism underlying the octopamine-induced synaptic growth in octopaminergic neurons. I discovered that this positive-feedback mechanism depends on an octopamine autoreceptor, Octß2R. This receptor in turn activates a cAMP- and CREB-dependent pathway that is required in the octopamine-induction of synaptopods. Furthermore, I demonstrated that this octopaminergic autoregulatory mechanism is necessary for the larva to properly increase its locomotor activity during starvation.
Thirdly, I investigated the possibility that type II innervation might regulate type I synaptic growth through octopamine. We found that ablation, blocking of type II activity, or the absence of octopamine results in reduced type I outgrowth, and this paracrine signaling is mediated by Octß2R which is also present in type I motorneurons.
Lastly, the function of another octopamine receptor, Octß1R, was examined. In contrast to Octß2R, Octß1R is inhibitory to synaptic growth. I demonstrated that the inhibitory effect of this receptor is likely accomplished through the inhibitory G-protein Goα. Similar to Octß2R, Octß1R also regulates the synaptic growth of both type I and type II motorneurons in a cell-autonomous manner. The inhibitory function of this receptor potentially breaks the positive feedback loop mediated by Octß2R, allowing the animal to reset its neurons when the environment is favorable.
In summary, the research presented in this thesis has unraveled both autoregulatory and paracrine mechanisms in which octopamine modulates synaptic and behavior plasticity through excitatory and inhibitory receptors.
47
Speed, Haley E. "Changes in short-term facilitation are opposite at Schaffer collateral and Temporoammonic CA1 synapses in the developing rat hippocampus." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/speed.pdf.
Full text
48
Holohean, Alice Marie. "A Quantitative Description of the Interaction of Enhancement and Depression of Transmitter Release at the Neuromuscular Junction." Scholarly Repository, 2007. http://scholarlyrepository.miami.edu/oa_dissertations/19.
Full textAbstract:
Synaptic transmission alters the strength of the postsynaptic potential, through a process called short-term synaptic plasticity (STP). In this study, endplate potentials (EPPs) from the frog neuromuscular junction were used to resolve and quantify the presynaptic components involved in enhancement and depression of transmitter release during repetitive stimulation under normal quantal release conditions (2 mM Ca2+, 1mM Mg2+). During trains of stimulation given between 10 - 200 Hz, the amplitude of the EPPs first increased then decreased; a maximum increase of 77% was produced after 2-4 stimuli. EPP amplitudes began to increase at ~ 20 Hz, were maximal at ~ 55 Hz, and thereafter, decreased as the rate of stimulation increased. The integrated total release after 25 stimuli was little changed across frequencies between 10 - 100 Hz. EPPs ran down in two phases: a fast phase, attributed to the depletion of a readily releasable pool (RRP) of synaptic vesicles, followed by a slow phase, attributed to the depletion of vesicles from a depot pool (DP). Depletion of the readily releasable pool of synaptic vesicles (RRP) was determined by quantifying release under the fast and slow time rundowns and subtracting the number of vesicles associated with mobilization to the RRP from the total number of vesicles released during stimulation trains of 50 impulses. Impulses were delivered at 12 different rates ranging from 50 to 200 /s. Estimates of the number of vesicles released from the RRP increased with frequency of stimulation until maximal depletion levels of 5500 - 6000 vesicles were reached at stimulation rates between 90-130/s, assuming a control quantal content of 200 vesicles released per impulse. Depletion was less at lower frequencies when the number of stimuli delivered was identical. When the RRP maximally depleted, release was inversely related to stimulation rate, as would be expected if mobilization from the depot pool was the sole determinate of release during the slow phase. An equation constructed from four known components of enhancement and two components of depression - the depletion of vesicles from a readily releasable pool (RRP) and from the depot pool (DP) that refills the RRP, was used to fit and then simulate EPPs obtained during trains using different patterns of stimulation and varying amounts of extracellular Ca2+; the decay time constant parameters of enhancement, numerically derived from the observed data, were fixed at tau ~ 46, 220, 1600, and 20000 ms. The number of components of enhancement necessary to approximate the data decreased, from four in low (0.14 - 0.2mM) extracellular Ca2+, to one (tau ~ 46 ms) in 2.0 mM extracellular Ca2+, but four components of enhancement were necessary to fit the data when the amplitude of the EPP was not depressed below the control amplitude. This model was able to predict within ~ 3 % EPP amplitudes over a 10-fold range of frequency and Ca2+ concentration.
49
Takeda, Michiko [Verfasser], Hiroshi [Akademischer Betreuer] Kawabe, Nils [Akademischer Betreuer] Brose, and Andreas [Akademischer Betreuer] Stumpner. "The Role of the E3 Ubiquitin Ligases Nedd4-1 and Nedd4-2 in Synaptic Transmission and Plasticity / Michiko Takeda. Gutachter: Nils Brose ; Andreas Stumpner. Betreuer: Hiroshi Kawabe." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/104430779X/34.
Full text
50
Leonardon, Benjamin. "Modulation de la transmission synaptique inhibitrice par les récepteurs NMDA dans la corne dorsale de la moelle épinière de souris." Thesis, Strasbourg, 2020. http://www.theses.fr/2020STRAJ006.
Full textAbstract:
Dans les cornes dorsales (CD), la transmission synaptique inhibitrice joue un rôle clef dans le traitement des informations nociceptives. Cette inhibition peut subir des changements plastiques menant à des symptômes d’hyperalgésie et d’allodynie liés aux douleurs neuropathiques. Dans les CD, les récepteurs NMDA sont recrutés suite à une lésion nerveuse, bien que leur rôle dans les phénomènes de plasticités de la synapse excitatrice soit bien étudié, leur implication dans la plasticité de l’inhibition spinale reste peu connue. Mon projet de thèse a visé à déterminer l’effet de l’activation des récepteurs NMDA sur l’inhibition synaptique spinale en condition normale et en condition de douleur neuropathique. Pour cela nous utilisons des approches d’électrophysiologies sur tranches aiguës de moelle épinière de souris adultes. Les résultats obtenus ont permis d'améliorer la compréhension des mécanismes de modulation et plasticité de l’inhibition au sein du réseau nociceptif spinalIn the dorsal horn (DH) of the spinal cord, inhibitory synaptic transmission plays a key role in the processing of nociceptive information. This inhibition can display plastic changes linked with hyperalgesia and allodynia associated with neuropathic pain. In the DH, NMDA receptors are recruited following a nerve injury. Although their role in plastic phenomenon is well established, little is known about their involvement in spinal inhibition plasticity. My research project aims at studying the effect of NMDA receptor activation on spinal synaptic inhibition in a normal state and during neuropathic pain. To do so we used an electrophysiological approach on acute spinal cord slices of adult mice. Results obtained allow a better understanding of the mechanism underlying the modulation and plasticity of inhibitory transmission within the spinal nociceptive network